Search results for: evolution mechanism

Authors: Ravi Raj, Louis Chiu, Deepak Marla, Aijun Huang

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Hybridization of the directed laser deposition (DLD) process using an in-situ micro-roller to impart a vertical compressive load on the deposited bead at elevated temperatures can relieve tensile residual stresses incurred in the process. To investigate this stress relief mechanism and its relationship with the in-situ rolling parameters, a fully coupled dynamic thermo-mechanical model is presented in this study. A single bead deposition of Ti-6Al-4V alloy with an in-situ roller made of mild steel moving at a constant speed with a fixed nominal bead reduction is simulated using the explicit solver of the finite element software, Abaqus. The thermal model includes laser heating during the deposition process and the heat transfer between the roller and the deposited bead. The laser heating is modeled using a moving heat source with a Gaussian distribution, applied along the pre-formed bead’s surface using the VDFLUX Fortran subroutine. The bead’s cross-section is assumed to be semi-elliptical. The interfacial heat transfer between the roller and the bead is considered in the model. Besides, the roller is cooled internally using axial water flow, considered in the model using convective heat transfer. The mechanical model for the bead and substrate includes the effects of rolling along with the deposition process, and their elastoplastic material behavior is captured using the J2 plasticity theory. The model accounts for strain, strain rate, and temperature effects on the yield stress based on Johnson-Cook’s theory. Various aspects of this material behavior are captured in the FE software using the subroutines -VUMAT for elastoplastic behavior, VUHARD for yield stress, and VUEXPAN for thermal strain. The roller is assumed to be elastic and does not undergo any plastic deformation. Also, contact friction at the roller-bead interface is considered in the model. Based on the thermal results of the bead, the distance between the roller and the deposition nozzle (roller o set) can be determined to ensure rolling occurs around the beta-transus temperature for the Ti-6Al-4V alloy. It is identified that roller offset and the nominal bead height reduction are crucial parameters that influence the residual stresses in the hybrid process. The results obtained from a simulation at roller offset of 20 mm and nominal bead height reduction of 7% reveal that the tensile residual stresses decrease to about 52% due to in-situ rolling throughout the deposited bead. This model can be used to optimize the rolling parameters to minimize the residual stresses in the hybrid DLD process with in-situ micro-rolling.

Keywords: directed laser deposition, finite element analysis, hybrid in-situ rolling, thermo-mechanical model

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Authors: Nima Samie, Sekaran Muniandy, Zahurin Mohamed, M. S. Kanthimathi

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Although number of indole containing compounds have been reported to have anticancer properties in vitro but only a few of them show potential as anticancer compounds in vivo. The current study was to evaluate the mechanism of cytotoxicity of selected indolic compound in vivo and in vitro. In this context, we determined the potency of the compound in the induction of apoptosis, cell cycle arrest, and cytoskeleton rearrangement. HT-29, WiDr, CCD-18Co, human monocyte/macrophage CRL-9855, and B lymphocyte CCL-156 cell lines were used to determine the IC50 of the compound using the MTT assay. Analysis of apoptosis was carried out using immunofluorescence, acridine orange/ propidium iodide double staining, Annexin-V-FITC assay, evaluation of the translocation of NF-kB, oxygen radical antioxidant capacity, quenching of reactive oxygen species content, measurement of LDH release, caspase-3/-7, -8 and -9 assays and western blotting. The cell cycle arrest was examined using flowcytometry and gene expression was assessed using qPCR array. Results displayed a potent suppressive effect on HT-29 and WiDr after 24 h of treatment with IC50 value of 2.52±0.34 µg/ml and 2.13±0.65 µg/ml respectively. This cytotoxic effect on normal, monocyte/macrophage and B-cells was insignificant. Dipping in the mitochondrial membrane potential and increased release of cytochrome c from the mitochondria indicated induction of the intrinsic apoptosis pathway by the compound. Activation of this pathway was further evidenced by significant activation of caspase-9 and 3/7. The compound was also shown to activate the extrinsic pathways of apoptosis via activation of caspase-8 which is linked to the suppression of NF-kB translocation to the nucleus. Cell cycle arrest in the G1 phase and up-regulation of glutathione reductase, based on excessive ROS production were also observed. These findings were further investigated for inhibitory efficiency of the compound on colonic aberrant crypt foci in male rats. Rats were divided in to 5 groups: vehicle, cancer control, positive control groups and the groups treated with 25 and 50 mg/kg of compounds for 10 weeks. Administration of compound suppressed total colonic ACF formation up to 73.4%. The results also showed that treatment with the compound significantly reduced the level of malondialdehyde while increasing superoxide dismutase and catalase activities. Furthermore, the down-regulation of PCNA and Bcl2 and the up-regulation of Bax was confirmed by immunohistochemical staining. The outcome of this study suggest sthat the indolic compound is a potent anti-cancer agent against colon cancer and can be further evaluated by animal trial.

Keywords: indolic compound, chemoprevention, crypt, azoxymethane, colon cancer

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Authors: Farzaneh Sasanpour, Saeed Amini Varaki

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Resilience is an important goal for cities as urban areas face an increasing range of challenges in the 21st century; therefore, according to the characteristics of risks, adopting an approach that responds to sensitive conditions in the risk management process is the resilience of cities. In the meantime, most of the resilience assessments have dealt with natural hazards and less attention has been paid to pandemics.In the covid-19 pandemic, the country of Iran and especially the metropolis of Tehran, was not immune from the crisis caused by its effects and consequences and faced many challenges. One of the methods that can increase the resilience of Tehran's metropolis against possible crises in the future is future studies. This research is practical in terms of type. The general pattern of the research will be descriptive-analytical and from the point of view that it is trying to communicate between the components and provide urban resilience indicators with pandemic crises and explain the scenarios, its future studies method is exploratory. In order to extract and determine the key factors and driving forces effective on the resilience of Tehran's urban areas against pandemic crises (Covid-19), the method of structural analysis of mutual effects and Micmac software was used. Therefore, the primary factors and variables affecting the resilience of Tehran's urban areas were set in 5 main factors, including physical-infrastructural (transportation, spatial and physical organization, streets and roads, multi-purpose development) with 39 variables based on mutual effects analysis. Finally, key factors and variables in five main areas, including managerial-institutional with five variables; Technology (intelligence) with 3 variables; economic with 2 variables; socio-cultural with 3 variables; and physical infrastructure, were categorized with 7 variables. These factors and variables have been used as key factors and effective driving forces on the resilience of Tehran's urban areas against pandemic crises (Covid-19), in explaining and developing scenarios. In order to develop the scenarios for the resilience of Tehran's urban areas against pandemic crises (Covid-19), intuitive logic, scenario planning as one of the future research methods and the Global Business Network (GBN) model were used. Finally, four scenarios have been drawn and selected with a creative method using the metaphor of weather conditions, which is indicative of the general outline of the conditions of the metropolis of Tehran in that situation. Therefore, the scenarios of Tehran metropolis were obtained in the form of four scenarios: 1- solar scenario (optimal governance and management leading in smart technology) 2- cloud scenario (optimal governance and management following in intelligent technology) 3- dark scenario (optimal governance and management Unfavorable leader in intelligence technology) 4- Storm scenario (unfavorable governance and management of follower in intelligence technology). The solar scenario shows the best situation and the stormy scenario shows the worst situation for the Tehran metropolis. According to the findings obtained in this research, city managers can, in order to achieve a better tomorrow for the metropolis of Tehran, in all the factors and components of urban resilience against pandemic crises by using future research methods, a coherent picture with the long-term horizon of 2050, from the path Provide urban resilience movement and platforms for upgrading and increasing the capacity to deal with the crisis. To create the necessary platforms for the realization, development and evolution of the urban areas of Tehran in a way that guarantees long-term balance and stability in all dimensions and levels.

Keywords: future research, resilience, crisis, pandemic, covid-19, Tehran

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Authors: Jana Andzane, Gunta Kunakova, Margarita Baitimirova, Mikelis Marnauza, Floriana Lombardi, Donats Erts

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Bismuth selenide (Bi₂Se₃) is known as a narrow band gap semiconductor with pronounced thermoelectric (TE) and topological insulator (TI) properties. Unique TI properties offer exciting possibilities for fundamental research as observing the exciton condensate and Majorana fermions, as well as practical application in spintronic and quantum information. In turn, TE properties of this material can be applied for wide range of thermoelectric applications, as well as for broadband photodetectors and near-infrared sensors. Nanostructuring of this material results in improvement of TI properties due to suppression of the bulk conductivity, and enhancement of TE properties because of increased phonon scattering at the nanoscale grains and interfaces. Regarding TE properties, crystallographic growth direction, as well as orientation of the nanostructures relative to the growth substrate, play significant role in improvement of TE performance of nanostructured material. For instance, Bi₂Se₃ layers consisting of randomly oriented nanostructures and/or of combination of them with planar nanostructures show significantly enhanced in comparison with bulk and only planar Bi₂Se₃ nanostructures TE properties. In this work, a catalyst-free vapour-solid deposition technique was applied for controlled obtaining of different types of Bi₂Se₃ nanostructures and continuous nanostructured layers for targeted applications. For example, separated Bi₂Se₃ nanoplates, nanobelts and nanowires can be used for investigations of TI properties; consisting from merged planar and/or randomly oriented nanostructures Bi₂Se₃ layers are useful for applications in heat-to-power conversion devices and infrared detectors. The vapour-solid deposition was carried out using quartz tube furnace (MTI Corp), equipped with an inert gas supply and pressure/temperature control system. Bi₂Se₃ nanostructures/nanostructured layers of desired type were obtained by adjustment of synthesis parameters (process temperature, deposition time, pressure, carrier gas flow) and selection of deposition substrate (glass, quartz, mica, indium-tin-oxide, graphene and carbon nanotubes). Morphology, structure and composition of obtained Bi₂Se₃ nanostructures and nanostructured layers were inspected using SEM, AFM, EDX and HRTEM techniques, as well as home-build experimental setup for thermoelectric measurements. It was found that introducing of temporary carrier gas flow into the process tube during the synthesis and deposition substrate choice significantly influence nanostructures formation mechanism. Electrical, thermoelectric, and topological insulator properties of different types of deposited Bi₂Se₃ nanostructures and nanostructured coatings are characterized as a function of thickness and discussed.

Keywords: bismuth seleinde, nanostructures, topological insulator, vapour-solid deposition

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Authors: Vivian Caroline Koerbel Dombrowski

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Armed conflicts have always meant the ultimate expression of power and at the same time, lack of understanding among nations. Cities were destroyed, people were killed, assets were devastated. But these are not only the loss of a war: the environmental damage comes to be considered immeasurable losses in the short, medium and long term. And this is because no nation wants to bear that cost. They invest in military equipment, training, technical equipment but the environmental account yet finds gaps in international law. Considering such a generalization in rights protection, many nations are at imminent danger in a conflict if the water will be used as a mass weapon, especially if we consider important rivers such as Jordan, Euphrates and Nile. The top three international documents were analyzed on the subject: the Stockholm Convention (1972), Additional Protocol I to the Geneva Convention (1977) and the Rome Statute (1998). Indeed, some references are researched in doctrine, especially scientific articles, to substantiate with consistent data about the extent of the damage, historical factors and decisions which have been successful. However, due to the lack of literature about this subject, the research tends to be exhaustive. From the study of the indicated material, it was noted that international law - humanitarian and environmental - calls in some of its instruments the environmental protection in war conflicts, but they are generic and vague rules that do not define exactly what is the environmental damage , nor sets standards for measure them. Taking into account the mains conflicts of the century XX: World War II, the Vietnam War and the Gulf War, one must realize that the environmental consequences were of great rides - never deactivated landmines, buried nuclear weapons, armaments and munitions destroyed in the soil, chemical weapons, not to mention the effects of some weapons when used (uranium, agent Orange, etc). Extending the search for more recent conflicts such as Afghanistan, it is proven that the effects on health of the civilian population were catastrophic: cancer, birth defects, and deformities in newborns. There are few reports of nations that, somehow, repaired the damage caused to the environment as a result of the conflict. In the pitch of contemporary conflicts, many nations fear that water resources are used as weapons of mass destruction, because once contaminated - directly or indirectly - can become a means of disguised genocide side effect of military objective. In conclusion, it appears that the main international treaties governing the subject mention the concern for environmental protection, however leave the normative specifications vacancies necessary to effectively there is a prevention of environmental damage in armed conflict and, should they occur, the repair of the same. Still, it appears that there is no protection mechanism to safeguard natural resources and avoid them to become a mass destruction weapon.

Keywords: armed conflicts, criminal liability, environmental damages, humanitarian law, mass weapon

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Authors: Nino Pailodze, Malkhaz Sulashvili, Vladimer Kekenadze, Tea Khutsishvili, Irma Makharashvili, Aleksandre Kekenadze

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In the nearest future among the important problems which Georgia has solve the most important is economic stability, that bases on fiscal policy and the proper definition of the its directions. The main source of the Budget revenue is the national income. The State uses taxes, loans and emission in order to create national income, were the principal weapon are taxes. As well as fiscal function of the fulfillment of the budget, tax systems successfully implement economic and social development and the regulatory functions of foreign economic relations. A tax is a mandatory, unconditional monetary payment to the budget made by a taxpayer in accordance with this Code, based on the necessary, nonequivalent and gratuitous character of the payment. Taxes shall be national and local. National taxes shall be the taxes provided for under this Code, the payment of which is mandatory across the whole territory of Georgia. Local taxes shall be the taxes provided for under this Code, introduced by normative acts of local self-government representative authorities (within marginal rates), the payment of which is mandatory within the territory of the relevant self-governing unit. National taxes have the leading role in tax systems, but also the local taxes have an importance role in tax systems. Exactly in the means of local taxes, the most part of the budget is formatted. National taxes shall be: income tax, profit tax, value added tax (VAT), excise tax, import duty, property tax shall be a local tax The property tax is one of the significant taxes in Georgia. The paper deals with the taxation mechanism that has been operated in Georgia. The above mention has the great influence in financial accounting. While comparing foreign legislation towards Georgian legislation we discuss the opportunity of using their experience. Also, we suggested recommendations in order to improve the tax system in financial accounting. In addition to accounting, which is regulated according the International Accounting Standards we have tax accounting, which is regulated by the Tax Code, various legal orders / regulations of the Minister of Finance. The rules are controlled by the tax authority, Revenue Service. The tax burden from the tax values are directly related to expenditures of the state from the emergence of the first day. Fiscal policy of the state is as well as expenditure of the state and decisions of taxation. In order to get the best and the most effective mobilization of funds, Government’s primary task is to decide the kind of taxation rules. Tax function is to reveal the substance of the act. Taxes have the following functions: distribution or the fiscal function; Control and regulatory functions. Foreign tax systems evolved in the different economic, political and social conditions influence. The tax systems differ greatly from each other: taxes, their structure, typing means, rates, the different levels of fiscal authority, the tax base, the tax sphere of action, the tax breaks.

Keywords: international accounting standards, financial accounting, tax systems, financial obligations

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Authors: Iliyasu Musa Omoyine, Musa Sunday Abraham, Oladele Sunday Blessing, Iliya Ibrahim Abdullahi, Ibegbu Augustine Oseloka, Nuhu Nana-Hawau, Animoku Abdulrazaq Amoto, Yusuf Abdullateef Onoruoiza, Sambo Sohnap James, Akpulu Steven Peter, Ajayi Abayomi

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The neuroprotective role of inflammation from detrimental intrinsic and extrinsic factors has been reported. However, the overactivation of astrocytes and microglia due to lead toxicity produce excessive pro-inflammatory cytokines, mediating neurodegenerative diseases. The present study investigated the mitigatory effects of quercetin on neuroinflammation, correlating with memory function in lead-exposed rats. In this study, Wistar rats were administered orally with Quercetin (Q: 60 mg/kg) and Succimer as a standard drug (S: 10 mg/kg) for 21 days after lead exposure (Pb: 125 mg/kg) of 21 days or in combination with Pb, once daily for 42 days. Working and reference memory was assessed using an Eight-arm radial water maze (8-ARWM). The changes in brain lead level, the neuronal nitric oxide synthase (nNOS) activity, and the level of neuroinflammatory markers such as tumour necrosis factor-alpha (TNF-α) and Interleukin 1 Beta (IL-1β) were determined. Immunohistochemically, astrocyte expression was evaluated. The results showed that the brain level of lead was increased significantly in lead-exposed rats. The expression of astrocytes increased in the CA3 and CA1 regions of the hippocampus, and the levels of brain TNF-α and IL-1β increased in lead-exposed rats. Lead impaired reference and working memory by increasing reference memory errors and working memory incorrect errors in lead-exposed rats. However, quercetin treatment effectively improved memory and inhibited neuroinflammation by reducing astrocytes’ expression and the levels of TNF-α and IL-1β. The expression of astrocytes and the levels of TNF-α and IL-1β correlated with memory function. The possible explanation for quercetin’s anti-neuroinflammatory effect is that it modulates the activity of cellular proteins involved in the inflammatory response; inhibits the transcription factor of nuclear factor-kappa B (NF-κB), which regulates the expression of proinflammatory molecules; inhibits kinases required for the synthesis of Glial fibrillary acidic protein (GFAP) and modifies the phosphorylation of some proteins, which affect the structure and function of intermediate filament proteins; and, lastly, induces Cyclic-AMP Response Element Binding (CREB) activation and neurogenesis as a compensatory mechanism for memory deficits and neuronal cell death. In conclusion, the levels of neuroinflammatory markers negatively correlated with memory function. Thus, quercetin may be a promising therapy in neuroinflammation and memory dysfunction in populations prone to lead exposure.

Keywords: lead, quercetin, neuroinflammation, memory

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Authors: Mahmut Sozmen, Alparslan Kadir Devrim, Yonca Betil Kabak, Tuba Devrim

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Acute myocardial infarction is the leading cause of deaths in the worldwide. Mature cardiomyocytes do not have the ability to regenerate instead fibrous tissue proliferate and granulation tissue to fill out. Periostin is an extracellular matrix protein from fasciclin family and it plays an important role in the cell adhesion, migration, and growth of the organism. Periostin prevents apoptosis while stimulating cardiomyocytes. The main objective of this project is to investigate the effects of the recombinant murine periostin peptide administration for the cardiomyocyte regeneration in a rat model of acute myocardial infarction. The experiment was performed on 84 male rats (6 months old) in 4 group each contains 21 rats. Saline applied subcutaneously (1 ml/kg) two times with 24 hours intervals to the rats in control group (Group 1). Recombinant periostin peptide (1 μg/kg) dissolved in saline applied intraperitoneally in group 2 on 1, 3, 7, 14 and 21. days on same dates in group 4. Isoproterenol dissolved in saline applied intraperitoneally (85mg/kg/day) two times with 24 hours intervals to the groups 3 and 4. Rats in group 4 further received recombinant periostin peptide (1 μg/kg) dissolved in saline intraperitoneally starting one day after the final isoproterenol administration on days 1, 3, 7, 14 and 21. Following the final application of periostin rats continued to feed routinely with pelleted chow and water ad libitum for further seven days. At the end of 7th day rats sacrificed, blood and heart tissue samples collected for the immunohistochemical and biochemical analysis. Angiogenesis in response to tissue damage, is a highly dynamic process regulated by signals from the surrounding extracellular matrix and blood serum. In this project, VEGF, ANGPT, bFGF, TGFβ are the key factors that contribute to cardiomyocyte regeneration were investigated. Additionally, the relationship between mitosis and apoptosis (Bcl-2, Bax, PCNA, Ki-67, Phopho-Histone H3), cell cycle activators and inhibitors (Cyclin D1, D2, A2, Cdc2), the origin of regenerating cells (cKit and CD45) were examined. Present results revealed that periostin stimulated cardiomyocye cell-cycle re-entry in both normal and MCA damaged cardiomyocytes and increased angiogenesis. Thus, periostin contributes to cardiomyocyte regeneration during the healing period following myocardial infarction which provides a better understanding of its role of this mechanism, improving recovery rates and it is expected to contribute the lack of literature on this subject. Acknowledgement: This project was financially supported by Turkish Scientific Research Council- Agriculture, Forestry and Veterinary Research Support Group (TUBİTAK-TOVAG; Project No: 114O734), Ankara, TURKEY.

Keywords: cardiotoxicity, immunohistochemistry, isoproterenol, periostin

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Authors: Syed Asif Hassan, Tabrej Khan

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Tuberculosis (TB) caused by bacillus Mycobacterium tuberculosis (Mtb) continues to take a disturbing toll on human life and healthcare facility worldwide. The global burden of TB remains enormous. The alarming rise of multi-drug resistant strains of Mycobacterium tuberculosis calls for an increase in research efforts towards the development of new target specific therapeutics against diverse strains of M. tuberculosis. Therefore, the discovery of new molecular scaffolds targeting new drug sites should be a priority for a workable plan for fighting resistance in Mycobacterium tuberculosis (Mtb). Mtb non-acylated lipoprotein LprG (Rv1411c) has a Toll-like receptor 2 (TLR2) agonist actions that depend on its association with triacylated glycolipids binding specifically with the hydrophobic pocket of Mtb LprG lipoprotein. The detection of a glycolipid carrier function has important implications for the role of LprG in Mycobacterial physiology and virulence. Therefore, considering the pivotal role of glycolipids in mycobacterial physiology and host-pathogen interactions, designing competitive antagonist (chemotherapeutics) ligands that competitively bind to glycolipid binding domain in LprG lipoprotein, will lead to inhibition of tuberculosis infection in humans. In this study, a unified approach involving ligand-based virtual screening protocol USRCAT (Ultra Shape Recognition) software and molecular docking studies using Auto Dock Vina 1.1.2 using the X-ray crystal structure of Mtb LprG protein was implemented. The docking results were further confirmed by DSX (DrugScore eXtented), a robust program to evaluate the binding energy of ligands bound to the Ligand binding domain of the Mtb LprG lipoprotein. The ligand, which has the higher hypothetical affinity, also has greater negative value. Based on the USRCAT, Lipinski’s values and molecular docking results, [(2R)-2,3-di(hexadecanoyl oxy)propyl][(2S,3S,5S,6R)-3,4,5-trihydroxy-2,6-bis[[(2R,3S,4S,5R,6S)-3,4,5-trihydroxy-6 (hydroxymethyl)tetrahydropyran-2-yl]oxy]cyclohexyl] phosphate (XPX) was confirmed as a promising drug-like lead compound (antagonist) binding specifically to the hydrophobic domain of LprG protein with affinity greater than that of PIM2 (agonist of LprG protein) with a free binding energy of -9.98e+006 Kcal/mol and binding affinity of -132 Kcal/mol, respectively. A further, in vitro assay of this compound is required to establish its potency in inhibiting molecular evasion mechanism of MTB within the infected host macrophages. These results will certainly be helpful in future anti-TB drug discovery efforts against Multidrug-Resistance Tuberculosis (MDR-TB).

Keywords: antagonist, agonist, binding affinity, chemotherapeutics, drug-like, multi drug resistance tuberculosis (MDR-TB), RV1411c protein, toll-like receptor (TLR2)

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Authors: Ali Raza

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The dynamic landscape of communication has brought about significant advancements that intersect with the realms of public health and journalism. This abstract explores the evolving synergy between these fields, highlighting how their intersection has contributed to informed societies and improved public health outcomes. In the digital age, communication plays a pivotal role in shaping public perception, policy formulation, and collective action. Public health, concerned with safeguarding and improving community well-being, relies on effective communication to disseminate information, encourage healthy behaviors, and mitigate health risks. Simultaneously, journalism, with its commitment to accurate and timely reporting, serves as the conduit through which health information reaches the masses. Advancements in communication technologies have revolutionized the ways in which public health information is both generated and shared. The advent of social media platforms, mobile applications, and online forums has democratized the dissemination of health-related news and insights. This democratization, however, brings challenges, such as the rapid spread of misinformation and the need for nuanced strategies to engage diverse audiences. Effective collaboration between public health professionals and journalists is pivotal in countering these challenges, ensuring that accurate information prevails. The synergy between public health and journalism is most evident during public health crises. The COVID-19 pandemic underscored the pivotal role of journalism in providing accurate and up-to-date information to the public. However, it also highlighted the importance of responsible reporting, as sensationalism and misinformation could exacerbate the crisis. Collaborative efforts between public health experts and journalists led to the amplification of preventive measures, the debunking of myths, and the promotion of evidence-based interventions. Moreover, the accessibility of information in the digital era necessitates a strategic approach to health communication. Behavioral economics and data analytics offer insights into human decision-making and allow tailored health messages to resonate more effectively with specific audiences. This approach, when integrated into journalism, enables the crafting of narratives that not only inform but also influence positive health behaviors. Ethical considerations emerge prominently in this alliance. The responsibility to balance the public's right to know with the potential consequences of sensational reporting underscores the significance of ethical journalism. Health journalists must meticulously source information from reputable experts and institutions to maintain credibility, thus fortifying the bridge between public health and the public. As both public health and journalism undergo transformative shifts, fostering collaboration between these domains becomes essential. Training programs that familiarize journalists with public health concepts and practices can enhance their capacity to report accurately and comprehensively on health issues. Likewise, public health professionals can gain insights into effective communication strategies from seasoned journalists, ensuring that health information reaches a wider audience. In conclusion, the convergence of public health and journalism, facilitated by communication advancements, is a cornerstone of informed societies. Effective communication strategies, driven by collaboration, ensure the accurate dissemination of health information and foster positive behavior change. As the world navigates complex health challenges, the continued evolution of this synergy holds the promise of healthier communities and a more engaged and educated public.

Keywords: public awareness, journalism ethics, health promotion, media influence, health literacy

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Authors: Ana Cristina García-Luna Romero

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This document seeks to reflect on the urban project from its conceptual identity root. In the first instance, a proposal is made on how the city project is sustained from the conceptual root, from the logos: it opens a way to assimilate the imagination; what we imagine becomes a reality. In this way, firstly, the need to use language as a vehicle for transmitting the stories that sustain us as humanity can be deemed as an important social factor that enables us to social behavior. Secondly, the need to attend to the written language as a mechanism of power, as a means to consolidate a dominant ideology or a political position, is raised; as it served to carry out the modernization project, it is therefore addressed differences between the real and the literate city. Thus, the consolidated urban-architectural project is based on logos, the project, and planning. Considering the importance of materiality and its relation to subjective well-being contextualized from a socio-urban approach, we question ourselves into how we can look at something that is doubtful. From a philosophy perspective, the truth is considered to be nothing more than a matter of correspondence between the observer and the observed. To understand beyond the relative of the gaze, it is necessary to expose different perspectives since it depends on the understanding of what is observed and how it is critically analyzed. Therefore, the analysis of materiality, as a political field, takes a proposal based on this research in the principles in transgenesis: principle of communication, representativeness, security, health, malleability, availability of potentiality or development, conservation, sustainability, economy, harmony, stability, accessibility, justice, legibility, significance, consistency, joint responsibility, connectivity, beauty, among others. The (urban) human being acts because he wants to live in a certain way: in a community, in a fair way, with opportunity for development, with the possibility of managing the environment according to their needs, etc. In order to comply with this principle, it is necessary to design strategies from the principles in transgenesis, which must be named, defined, understood, and socialized by the urban being, the companies, and from themselves. In this way, the technical status of the city in the neoliberal present determines extraordinary conditions for reflecting on an almost emergency scenario created by the impact of cities that, far from being limited to resilient proposals, must aim at the reflection of the urban process that the present social model has generated. Therefore, can we rethink the paradigm of the perception of life quality in the current neoliberal model in the production of the character of public space related to the practices of being urban. What we are trying to do within this document is to build a framework to study under what logic the practices of the social system that make sense of the public space are developed, what the implications of the phenomena of the inscription of action and materialization (and its results over political action between the social and the technical system) are and finally, how we can improve the quality of life of individuals from the urban space.

Keywords: cities, nature, society, urban quality of life

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Authors: Ece A. Irmak, Amdulla O. Mekhrabov, M. Vedat Akdeniz

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There is a growing interest in the modeling and simulation of magnetic nanoalloys by various computational methods. Magnetic crystalline/amorphous nanoparticles (NP) are interesting materials from both the applied and fundamental points of view, as their properties differ from those of bulk materials and are essential for advanced applications such as high-performance permanent magnets, high-density magnetic recording media, drug carriers, sensors in biomedical technology, etc. As an important magnetic material, Fe-Ni based nanoalloys have promising applications in the chemical industry (catalysis, battery), aerospace and stealth industry (radar absorbing material, jet engine alloys), magnetic biomedical applications (drug delivery, magnetic resonance imaging, biosensor) and computer hardware industry (data storage). The physical and chemical properties of the nanoalloys depend not only on the particle or crystallite size but also on composition and atomic ordering. Therefore, computer modeling is an essential tool to predict structural, electronic, magnetic and optical behavior at atomistic levels and consequently reduce the time for designing and development of new materials with novel/enhanced properties. Although first-principles quantum mechanical methods provide the most accurate results, they require huge computational effort to solve the Schrodinger equation for only a few tens of atoms. On the other hand, molecular dynamics method with appropriate empirical or semi-empirical inter-atomic potentials can give accurate results for the static and dynamic properties of larger systems in a short span of time. In this study, structural evolutions, magnetic and electronic properties of Fe-Ni based nanoalloys have been studied by using molecular dynamics (MD) method in Large-scale Atomic/Molecular Massively Parallel Simulator (LAMMPS) and Density Functional Theory (DFT) in the Vienna Ab initio Simulation Package (VASP). The effects of particle size (in 2-10 nm particle size range) and temperature (300-1500 K) on stability and structural evolutions of amorphous and crystalline Fe-Ni bulk/nanoalloys have been investigated by combining molecular dynamic (MD) simulation method with Embedded Atom Model (EAM). EAM is applicable for the Fe-Ni based bimetallic systems because it considers both the pairwise interatomic interaction potentials and electron densities. Structural evolution of Fe-Ni bulk and nanoparticles (NPs) have been studied by calculation of radial distribution functions (RDF), interatomic distances, coordination number, core-to-surface concentration profiles as well as Voronoi analysis and surface energy dependences on temperature and particle size. Moreover, spin-polarized DFT calculations were performed by using a plane-wave basis set with generalized gradient approximation (GGA) exchange and correlation effects in the VASP-MedeA package to predict magnetic and electronic properties of the Fe-Ni based alloys in bulk and nanostructured phases. The result of theoretical modeling and simulations for the structural evolutions, magnetic and electronic properties of Fe-Ni based nanostructured alloys were compared with experimental and other theoretical results published in the literature.

Keywords: density functional theory, embedded atom model, Fe-Ni systems, molecular dynamics, nanoalloys

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Authors: Irina P. Starodubtseva, Aleksandr N. Pavlenko

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Quenching is a term generally accepted for the process of rapid cooling of a solid that is overheated above the thermodynamic limit of the liquid superheat. The main objective of many previous studies on quenching is to find a way to reduce the total time of the transient process. Computational experiments were performed to simulate quenching by a falling liquid nitrogen film of an extremely overheated vertical copper plate with a structured capillary-porous coating. The coating was produced by directed plasma spraying. Due to the complexities in physical pattern of quenching from chaotic processes to phase transition, the mechanism of heat transfer during quenching is still not sufficiently understood. To our best knowledge, no information exists on when and how the first stable liquid-solid contact occurs and how the local contact area begins to expand. Here we have more models and hypotheses than authentically established facts. The peculiarities of the quench front dynamics and heat transfer in the transient process are studied. The created numerical model determines the quench front velocity and the temperature fields in the heater, varying in space and time. The dynamic pattern of the running quench front obtained numerically satisfactorily correlates with the pattern observed in experiments. Capillary-porous coatings with straight and reverse orientation of crests are investigated. The results show that the cooling rate is influenced by thermal properties of the coating as well as the structure and geometry of the protrusions. The presence of capillary-porous coating significantly affects the dynamics of quenching and reduces the total quenching time more than threefold. This effect is due to the fact that the initialization of a quench front on a plate with a capillary-porous coating occurs at a temperature significantly higher than the thermodynamic limit of the liquid superheat, when a stable solid-liquid contact is thermodynamically impossible. Waves present on the liquid-vapor interface and protrusions on the complex micro-structured surface cause destabilization of the vapor film and the appearance of local liquid-solid micro-contacts even though the average integral surface temperature is much higher than the liquid superheat limit. The reliability of the results is confirmed by direct comparison with experimental data on the quench front velocity, the quench front geometry, and the surface temperature change over time. Knowledge of the quench front velocity and total time of transition process is required for solving practically important problems of nuclear reactors safety.

Keywords: capillary-porous coating, heat transfer, Leidenfrost phenomenon, numerical simulation, quenching

Procedia PDF Downloads 109

Authors: Amanda Gregorim Fernandes, Lorena Cardoso Cintra, Rosalia Santos Amorim Jesuino, Fabricia Paula De Faria, Marcio José Poças Fonseca

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Bioethanol is one of the most promising biofuels and able to replace fossil fuels and reduce its different environmental impacts and can be generated from various agroindustrial waste. The Brazil is in first place in bioethanol production to be the largest producer of sugarcane. The bagasse sugarcane (SCB) has lignocellulose which is composed of three major components: cellulose, hemicellulose and lignin. Cellulose is a homopolymer of glucose units connected by glycosidic linkages. Among all species of Penicillium, Penicillium echinulatum has been the focus of attention because they produce high quantities of cellulase and the mutant strain 9A02S1 produces higher enzyme levels compared to the wild. Among the cellulases, the cellobiohydrolases enzymes are the main components of the cellulolytic system of fungi, and are also responsible for most of the potential hydrolytic in enzyme cocktails for the industrial processing of plant biomass and several cellobiohydrolases Penicillium had higher specific activity against cellulose compared to CBH I from Trichoderma reesei. This fact makes it an interesting pattern for higher yields in the enzymatic hydrolysis, and also they are important enzymes in the hydrolysis of crystalline regions of cellulose. Therefore, finding new and more active enzymes become necessary. Meanwhile, β-glycosidases act on soluble substrates and are highly dependent on cellobiohydrolases and endoglucanases action to provide the substrate in the hydrolysis of the biomass, but the cellobiohydrolases and endoglucanases are highly dependent β-glucosidases to maintain efficient hydrolysis. Thus, there is a need to understand the structure-function relationships that govern the catalytic activity of cellulolytic enzymes to elucidate its mechanism of action and optimize its potential as industrial biocatalysts. To evaluate the enzyme β-glucosidase of Penicillium echinulatum (PeBGL1) the gene was synthesized from the assembly sequence from a library in induction conditions and then the PeBGL1 gene was cloned in the vector pPICZαA and transformed into P. pastoris GS115. After processing, the producers of PeBGL1 were analyzed for enzyme activity and protein profile where a band of approximately 100 kDa was viewed. It was also carried out the zymogram. In partial characterization it was determined optimum temperature of 50°C and optimum pH of 6,5. In addition, to increase the secreted recombinant PeBGL1 production by Pichia pastoris, three parameters of P. pastoris culture medium were analysed: methanol, nitrogen source concentrations and the inoculum size. A 23 factorial design was effective in achieving the optimum condition. Altogether, these results point to the potential application of this P. echinulatum β-glucosidase in hydrolysis of cellulose for the production of bioethanol.

Keywords: bioethanol, biotechnology, beta-glucosidase, penicillium echinulatum

Procedia PDF Downloads 218

Authors: Keigo Nishitani, Kohei Mizuta Mizuta, Kazuyoshi Kurita, Yukinori Taniguchi

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To establish mass production process of Ti capsule which has Fe powder inside as magnetic hyperthermia implant, we assumed that Ti thin sheet can be drawn into a φ1.0 mm die hole through the medium of Fe Powder and becomes outer shell of capsule. This study discusses mechanism of powder assisted deep drawing process by both of numerical simulation and experiment. Ti thin sheet blank was placed on die, and was covered by Fe powder layer without pressurizing. Then upper punch was indented on the Fe powder layer, and the blank can be drawn into die cavity as pressurized powder particles were extruded into die cavity from behind of the drawn blank. Distinct Element Method (DEM) has been used to demonstrate the process. To identify bonding parameters on Fe particles which are cohesion, tensile bond stress and inter particle friction angle, axial and diametrical compression failure test of Fe powder compact was conducted. Several density ratios of powder compacts in range of 0.70 - 0.85 were investigated and relationship between mean stress and equivalent stress was calculated with consideration of critical state line which rules failure criterion in consolidation of Fe powder. Since variation of bonding parameters with density ratio has been experimentally identified, and good agreement has been recognized between several failure tests and its simulation, demonstration of powder assisted sheet forming by using DEM becomes applicable. Results of simulation indicated that indent/drawing length of Ti thin sheet is promoted by smaller Fe particle size, larger indent punch diameter, lower friction coefficient between die surface and Ti sheet and certain degrees of die inlet taper angle. In the deep drawing test, we have made die-set with φ2.4 mm punch and φ1.0 mm die bore diameter. Pure Ti sheet with 100 μm thickness, annealed at 650 deg. C has been tested. After indentation, indented/drawn capsule has been observed by microscope, and its length was measured to discuss the feasibility of this capsulation process. Longer drawing length exists on progressive loading pass comparing with the case of single stroke loading. It is expected that progressive loading has an advantage of which extrusion of powder particle into die cavity with Ti sheet is promoted since powder particle layer can be rebuilt while the punch is withdrawn from the layer in each loading steps. This capsulation phenomenon is qualitatively demonstrated by DEM simulation. Finally, we have fabricated Ti capsule which has Fe powder inside for magnetic hyperthermia cancer care treatment. It is concluded that suggested method is possible to use the manufacturing of Ti capsule implant for magnetic hyperthermia cancer care.

Keywords: metal powder compaction, metal forming, distinct element method, cancer care, magnetic hyperthermia

Procedia PDF Downloads 261

Authors: Alexander A. Stakheev, Larisa V. Samokhvalova, Sergey K. Zavriev

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Fusarium fungi are among the most devastating plant pathogens distributed all over the world. Significant reduction of grain yield and quality caused by Fusarium leads to multi-billion dollar annual losses to the world agricultural production. These organisms can also cause infections in immunocompromised persons and produce the wide range of mycotoxins, such as trichothecenes, fumonisins, and zearalenone, which are hazardous to human and animal health. Identification of Fusarium fungi based on the morphology of spores and spore-forming structures, colony color and appearance on specific culture media is often very complicated due to the high similarity of these features for closely related species. Modern Fusarium taxonomy increasingly uses data of crossing experiments (biological species concept) and genetic polymorphism analysis (phylogenetic species concept). A number of novel Fusarium sibling species has been established using DNA barcoding techniques. Species recognition is best made with the combined phylogeny of intron-rich protein coding genes and ribosomal DNA sequences. However, the internal transcribed spacer of (ITS), which is considered to be universal DNA barcode for Fungi, is not suitable for genus Fusarium, because of its insufficient variability between closely related species and the presence of non-orthologous copies in the genome. Nowadays, the translation elongation factor 1 alpha (TEF1α) gene is the “gold standard” of Fusarium taxonomy, but the search for novel informative markers is still needed. In this study, we used two novel DNA markers, frataxin (FXN) and heat shock protein 90 (HSP90) to discover phylogenetic relationships between Fusarium species. Multilocus phylogenetic analysis based on partial sequences of TEF1α, FXN, HSP90, as well as intergenic spacer of ribosomal DNA (IGS), beta-tubulin (β-TUB) and phosphate permease (PHO) genes has been conducted for 120 isolates of 19 Fusarium species from different climatic zones of Russia and neighboring countries using maximum likelihood (ML) and maximum parsimony (MP) algorithms. Our analyses revealed that FXN and HSP90 genes could be considered as informative phylogenetic markers, suitable for evolutionary and taxonomic studies of Fusarium genus. It has been shown that PHO gene possesses more variable (22 %) and parsimony informative (19 %) characters than other markers, including TEF1α (12 % and 9 %, correspondingly) when used for elucidating phylogenetic relationships between F. avenaceum and its closest relatives – F. tricinctum, F. acuminatum, F. torulosum. Application of novel DNA barcodes confirmed the fact that F. arthrosporioides do not represent a separate species but only a subspecies of F. avenaceum. Phylogeny based on partial PHO and FXN sequences revealed the presence of separate cluster of four F. avenaceum strains which were closer to F. torulosum than to major F. avenaceum clade. The strain F-846 from Moldova, morphologically identified as F. poae, formed a separate lineage in all the constructed dendrograms, and could potentially be considered as a separate species, but more information is needed to confirm this conclusion. Variable sites in PHO sequences were used for the first-time development of specific qPCR-based diagnostic assays for F. acuminatum and F. torulosum. This work was supported by Russian Foundation for Basic Research (grant № 15-29-02527).

Keywords: DNA barcode, fusarium, identification, phylogenetics, taxonomy

Procedia PDF Downloads 295

Authors: Joanna Cydejko, Paulina Mika

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Hypersensitivity reactions are side effects of medications that resemble an allergic reaction. Anaphylaxis is a generalized, severe allergic reaction of the body caused by exposure to a specific agent at a dose tolerated by a healthy body. The most common causes of anaphylaxis are food (about 70%), Hymenoptera venoms (22%), and medications (7%), despite detailed diagnostics in 1% of people, the cause of the anaphylactic reaction was not indicated. Contrast media are anaphylactic agents of unknown mechanism. Hypersensitivity reactions can occur with both immunological and non-immunological mechanisms. Symptoms of anaphylaxis occur within a few seconds to several minutes after exposure to the allergen. Contrast agents are chemical compounds that make it possible to visualize or improve the visibility of anatomical structures. In the diagnosis of computed tomography, the preparations currently used are derivatives of the triiodide benzene ring. Pharmacokinetic and pharmacodynamic properties, i.e., their osmolality, viscosity, low chemotoxicity and high hydrophilicity, have an impact on better tolerance of the substance by the patient's body. In MRI diagnostics, macrocyclic gadolinium contrast agents are administered during examinations. The aim of this study is to present the results of the number and severity of anaphylactic reactions that occurred in patients in all age groups undergoing diagnostic imaging with intravenous administration of contrast agents. In non-ionic iodine CT and in macrocyclic gadolinium MRI. A retrospective assessment of the number of adverse reactions after contrast administration was carried out on the basis of data from the Department of Radiology of the University Clinical Center in Gdańsk, and it was assessed whether their different physicochemical properties had an impact on the incidence of acute complications. Adverse reactions are divided according to the severity of the patient's condition and the diagnostic method used in a given patient. Complications following the administration of a contrast medium in the form of acute anaphylaxis accounted for less than 0.5% of all diagnostic procedures performed with the use of a contrast agent. In the analysis period from January to December 2022, 34,053 CT scans and 15,279 MRI examinations with the use of contrast medium were performed. The total number of acute complications was 21, of which 17 were complications of iodine-based contrast agents and 5 of gadolinium preparations. The introduction of state-of-the-art contrast formulations was an important step toward improving the safety and tolerability of contrast agents used in imaging. Currently, contrast agents administered to patients are considered to be one of the best-tolerated preparations used in medicine. However, like any drug, they can be responsible for the occurrence of adverse reactions resulting from their toxic effects. The increase in the number of imaging tests performed with the use of contrast agents has a direct impact on the number of adverse events associated with their administration. However, despite the low risk of anaphylaxis, this risk should not be marginalized. The growing threat associated with the mass performance of radiological procedures with the use of contrast agents forces the knowledge of the rules of conduct in the event of symptoms of hypersensitivity to these preparations.

Keywords: anaphylactic, contrast medium, diagnostic, medical imagine

Procedia PDF Downloads 36

Authors: Ngoc Nguyen

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There is large plantation of Eucalyptus globulus established which has been grown to produce pulpwood. This resource is not suitable for the production of decorative products, principally due to low grades of wood and “dull” appearance but many trials have been already undertaken for the production of veneer and veneer-based engineered wood products, such as plywood and laminated veneer lumber (LVL). The manufacture of veneer-based products has been recently identified as an unprecedented opportunity to promote higher value utilisation of plantation resources. However, many uncertainties remain regarding the impacts of inferior wood quality of young plantation trees on product recovery and value, and with respect to optimal processing techniques. Moreover, the quality of veneer and veneer-based products is far from optimal as trees are young and have small diameters; and the veneers have the significant colour variation which affects to the added value of final products. Developing production methods which would enhance appearance of low-quality veneer would provide a great potential for the production of high-value wood products such as furniture, joinery, flooring and other appearance products. One of the methods of enhancing appearance of low quality veneer, developed in Italy, involves the production of multilaminar veneer, also named “reconstructed veneer”. An important stage of the multilaminar production is colouring the veneer which can be achieved by dyeing veneer with dyes of different colours depending on the type of appearance products, their design and market demand. Although veneer dyeing technology has been well advanced in Italy, it has been focused on poplar veneer from plantation which wood is characterized by low density, even colour, small amount of defects and high permeability. Conversely, the majority of plantation eucalypts have medium to high density, have a lot of defects, uneven colour and low permeability. Therefore, detailed study is required to develop dyeing methods suitable for colouring eucalypt veneers. Brown reactive dye is used for veneer colouring process. Veneers from sapwood and heartwood of two moisture content levels are used to conduct colouring experiments: green veneer and veneer dried to 12% MC. Prior to dyeing, all samples are treated. Both soaking (dipping) and vacuum pressure methods are used in the study to compare the results and select most efficient method for veneer dyeing. To date, the results of colour measurements by CIELAB colour system showed significant differences in the colour of the undyed veneers produced from heartwood part. The colour became moderately darker with increasing of Sodium chloride, compared to control samples according to the colour measurements. It is difficult to conclude a suitable dye solution used in the experiments at this stage as the variables such as dye concentration, dyeing temperature or dyeing time have not been done. The dye will be used with and without UV absorbent after all trials are completed using optimal parameters in colouring veneers.

Keywords: Eucalyptus globulus, veneer colouring/dyeing, multilaminar veneer, reactive dye

Procedia PDF Downloads 318

Authors: Alison L. Miles

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Almost all major financial institutions in the world suffered losses due to the financial crisis of 2007, but the extent varied widely. The causes of the crash of 2007 are well documented and predominately focus on the role and complexity of the financial markets. The dominant theme of the literature suggests the causes of the crash were a combination of globalization, financial sector innovation, moribund regulation and short termism. While these arguments are undoubtedly true, they do not tell the whole story. A key weakness in the current analysis is the lack of consideration of those leading the banks pre and during times of crisis. This purpose of this study is to examine the possible link between the leadership styles and characteristics of the CEO, CFO and chairman and the financial institutions that failed or needed recapitalization. As such, it contributes to the literature and debate on international financial crises and systemic risk and also to the debate on risk management and regulatory reform in the banking sector. In order to first test the proposition (p1) that there are prevalent leadership characteristics or traits in financial institutions, an initial study was conducted using a sample of the top 65 largest global banks and financial institutions according to the Banker Top 1000 banks 2014. Secondary data from publically available and official documents, annual reports, treasury and parliamentary reports together with a selection of press articles and analyst meeting transcripts was collected longitudinally from the period 1998 to 2013. A computer aided key word search was used in order to identify the leadership styles and characteristics of the chairman, CEO and CFO. The results were then compared with the leadership models to form a picture of leadership in the sector during the research period. As this resulted in separate results that needed combining, SPSS data editor was used to aggregate the results across the studies using the variables ‘leadership style’ and ‘company financial performance’ together with the size of the company. In order to test the proposition (p2) that there was a prevalent leadership style in the banks that failed and the proposition (P3) that this was different to those that did not, further quantitative analysis was carried out on the leadership styles of the chair, CEO and CFO of banks that needed recapitalization, were taken over, or required government bail-out assistance during 2007-8. These included: Lehman Bros, Merrill Lynch, Royal Bank of Scotland, HBOS, Barclays, Northern Rock, Fortis and Allied Irish. The findings show that although regulatory reform has been a key mechanism of control of behavior in the banking sector, consideration of the leadership characteristics of those running the board are a key factor. They add weight to the argument that if each crisis is met with the same pattern of popular fury with the financier, increased regulation, followed by back to business as usual, the cycle of failure will always be repeated and show that through a different lens, new paradigms can be formed and future clashes avoided.

Keywords: banking, financial crisis, leadership, risk

Procedia PDF Downloads 298

Authors: Eva Masson, Andrea Kübler

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Anxiety disorders (AD) are the most prevalent psychological disorders. However, far from most affected individuals are diagnosed and receive treatment. This gap is probably due to the diagnosis criteria, relying on symptoms (according to the DSM-5 definition) with no objective biomarker. Approach-avoidance conflict tasks are one common approach to simulate such disorders in a lab setting, with most of the paradigms focusing on the relationships between behavior and neurophysiology. Approach-avoidance conflict tasks typically place participants in a situation where they have to make a decision that leads to both positive and negative outcomes, thereby sending conflicting signals that trigger the Behavioral Inhibition System (BIS). Furthermore, behavioral validation of such paradigms adds credibility to the tasks – with overt conflict behavior, it is safer to assume that the task actually induced a conflict. Some of those tasks have linked asymmetrical frontal brain activity to induced conflicts and the BIS. However, there is currently no consensus for the direction of the frontal activation. The authors present here a modified version of the T-Maze paradigm, a motivational conflict desktop task, in which behavior is recorded simultaneously to the recording of high-density EEG (HD-EEG). Methods: In this within-subject design, HD-EEG and behavior of 35 healthy participants was recorded. EEG data was collected with a 128 channels sponge-based system. The motivational conflict desktop task consisted of three blocks of repeated trials. Each block was designed to record a slightly different behavioral pattern, to increase the chances of eliciting conflict. This variety of behavioral patterns was however similar enough to allow comparison of the number of trials categorized as ‘overt conflict’ between the blocks. Results: Overt conflict behavior was exhibited in all blocks, but always for under 10% of the trials, in average, in each block. However, changing the order of the paradigms successfully introduced a ‘reset’ of the conflict process, therefore providing more trials for analysis. As for the EEG correlates, the authors expect a different pattern for trials categorized as conflict, compared to the other ones. More specifically, we expect an elevated alpha frequency power in the left frontal electrodes at around 200ms post-cueing, compared to the right one (relative higher right frontal activity), followed by an inversion around 600ms later. Conclusion: With this comprehensive approach of a psychological mechanism, new evidence would be brought to the frontal asymmetry discussion, and its relationship with the BIS. Furthermore, with the present task focusing on a very particular type of motivational approach-avoidance conflict, it would open the door to further variations of the paradigm to introduce different kinds of conflicts involved in AD. Even though its application as a potential biomarker sounds difficult, because of the individual reliability of both the task and peak frequency in the alpha range, we hope to open the discussion for task robustness for neuromodulation and neurofeedback future applications.

Keywords: anxiety, approach-avoidance conflict, behavioral inhibition system, EEG

Procedia PDF Downloads 9

Authors: Sijie Chen, Xiaofang Chen, Juan Wang, Yingying Zhang, Yu Hong, Wanyu Zhuang, Xinxin Huang, Ping Ou, Longsheng Huang

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Purpose: Autistic symptom improvement can be observed in children treated with acupuncture, but the mechanism is still being explored. In the present study, we used scalp acupuncture to treat autism rat model, and then their improvement in the abnormal behaviors and specific mechanisms behind were revealed by detecting animal behaviors, analyzing the RNA sequencing of the prefrontal cortex(PFC), and observing the ultrastructure of PFC neurons under the transmission electron microscope. Methods: On gestational day 12.5, Wistar rats were given valproic acid (VPA) by intraperitoneal injection, and their offspring were considered to be reliable rat models of autism. They were randomized to VPA or VPA-acupuncture group (n=8). Offspring of Wistar pregnant rats that were simultaneously injected with saline were randomly selected as the wild-type group (WT). VPA_acupuncture group rats received acupuncture intervention at 23 days of age for 4 weeks, and the other two groups followed without intervention. After the intervention, all experimental rats underwent behavioral tests. Immediately afterward, they were euthanized by cervical dislocation, and their prefrontal cortex was isolated for RNA sequencing and transmission electron microscopy. Results: The main results are as follows: 1. Animal behavioural tests: VPA group rats showed more anxiety-like behaviour and repetitive, stereotyped behaviour than WT group rats. While VPA group rats showed less spatial exploration ability, activity level, social interaction, and social novelty preference than WT group rats. It was gratifying to observe that acupuncture indeed improved these abnormal behaviors of autism rat model. 2. RNA-sequencing: The three groups of rats differed in the expression and enrichment pathways of multiple genes related to synaptic function, neural signal transduction, and circadian rhythm regulation. Our experiments indicated that acupuncture can alleviate the major symptoms of ASD by improving these neurological abnormalities. 3. Under the transmission electron microscopy, several lysosomes and mitochondrial structural abnormalities were observed in the prefrontal neurons of VPA group rats, which were manifested as atrophy of the mitochondrial membran, blurring or disappearance of the mitochondrial cristae, and even vacuolization. Moreover, the number of synapses and synaptic vesicles was relatively small. Conversely, the mitochondrial structure of rats in the WT group and VPA_acupuncture was normal, and the number of synapses and synaptic vesicles was relatively large. Conclusion: Acupuncture effectively improved the abnormal behaviors of autism rat model and the ultrastructure of the PFC neurons, which might worked by improving their abnormal synaptic function, synaptic plasticity and promoting neuronal signal transduction.

Keywords: autism spectrum disorder, acupuncture, animal behavior, RNA sequencing, transmission electron microscope

Procedia PDF Downloads 17

Authors: Azar Mahmoudi

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Despite the rise of global anti-corruption movements and the strong emergence of international and national anti-corruption laws, corrupt practices are still prevalent in most places, and countries still struggle to translate these laws into practice. On the other hand, in most countries, political and economic elites oppose anti-corruption reforms. In such a situation, the role of external actors, like the other States, international organizations, and transnational actors, becomes essential. Among them, Transnational Corporations [TNCs] can develop their own regime-like framework to govern their internal activities, and through this, they can contribute to the regimes established by State actors to solve transnational issues. Among various regimes, TNCs may choose to comply with the transnational anti-corruption legal regime to avoid the cost of non-compliance with anti-corruption laws. As a result, they decide to strenghen their anti-corruption compliance as they expand into new overseas markets. Such a decision extends anti-corruption standards among their employees and third-party agents and within their projects across countries. To better address the challenges posed by corruption, TNCs have adopted a comprehensive anti-corruption toolkit. Among the various instruments, anti-corruption clauses have become one of the most anti-corruption means in international commercial agreements. Anti-corruption clauses, acting as a due diligence tool, can protect TNCs against the engagement of third-party agents in corrupt practices and further promote anti-corruption standards among businesses operating across countries. An anti-corruption clause allows parties to create a contractual commitment to exclude corrupt practices during the term of their agreement, including all levels of negotiation and implementation. Such a clause offers companies a mechanism to reduce the risk of potential corruption in their dealings with third parties while avoiding civil and administrative penalties. There have been few attempts to examine the role of anti-corruption clauses in the fight against corruption; therefore, this paper aims to fill this gap and examine anti-corruption clauses in a specific sector where corrupt practices are widespread and endemic, i.e., the petroleum industry. This paper argues that anti-corruption clauses are a positive step in ensuring that the petroleum industry operates in an ethical and transparent manner, helping to reducing the risk of corruption and promote integrity in this sector. Contractual anti-corruption clauses vary in terms of the types commitment, so parties have a wide range of options to choose from for their preferred clauses incorporated within their contracts. This paper intends to propose a categorization of anti-corruption clauses in the petroleum sector. It examines particularly the anti-corruption clauses incorporated in transnational hydrocarbon contracts published by the Resource Contract Portal, an online repository of extractive contracts. Then, this paper offers a quantitative assessment of anti-corruption clauses according to the types of contract, the date of conclusion, and the geographical distribution.

Keywords: anti-corruption, oil and gas, transnational corporations, due diligence, contractual clauses, hydrocarbon, petroleum sector

Procedia PDF Downloads 95

Authors: Tal Braverman Uriel, Tal Litvak Hirsch

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Background and Objectives: Little or only partial emphasis has been placed on exploring the complexity of consensual non-monogamous relationships. The term "polyamory" refers to consensual non-monogamy, and it is defined as having emotional and/or sexual relations simultaneously with two or more people, the consent and knowledge of all the partners concerned. Managing multiple romantic relationships with different people evokes more emotions, leads to more emotional conflicts arising from different interests, and demands practical strategies. An individual's transition from a monogamous lifestyle to a consensual non-monogamous lifestyle yields new challenges, accompanied by stress, uncertainty, and question marks, as do other life-changing events, such as divorce or transition to parenthood. The study examines both the process of transition and adaptation to a consensually non-monogamous relationship, as well as the coping mechanism involved in the daily conduct of this lifestyle. The research focuses on understanding the consequences, challenges, and coping methods from a personal, marital, and familial point of view and focuses on 40 middle-aged individuals (20 men and 20 women ages 40-60). The research sheds light on a way of life that has not been previously studied in Israel and is still considered unacceptable. Theories of crisis (e.g., as Folkman and Lazarus) were applied, and as a result, a deeper understanding of the subject was reached, all while focusing on multiple aspects of dealing with stress. The basic research question examines the consequences of entering a polyamorous life from a personal point of view as an individual, partner, and parent and the ways of coping with these consequences. Method: The research is conducted with a narrative qualitative approach in the interpretive paradigm, including semi-structured in-depth interviews. The method of analysis is thematic. Results: The findings indicate that in most cases, an individual's motivation to open the relationship is mainly a longing for better sexuality and for an added layer of excitement to their lives. Most of the interviewees were assisted by their spouses in the process, as well as by social networks and podcasts on the subject. Some of them therapeutic professionals from the field are helpful. It also clearly emerged that among those who experienced acute emotional crises with the primary partner or painful separations from secondary partners, all believed polyamory to be the adequate way of life for them. Finally, a key resource for managing tension and stress is the ability to share and communicate with the primary partner. Conclusions: The study points to the challenges and benefits of a non-monogamous lifestyle as well as the use of coping mechanisms and resources that are consistent with the existing theory and research in the field in the context of life changes. The study indicates the need to expand the research canvas in the future in the context of parenting and the consequences for children.

Keywords: a-monogamy, consent, family, stress, tension

Procedia PDF Downloads 46

Authors: N. Renuka, R. Ramesh Babu, N. Vijayan

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Ion beams play a significant role in the process of tuning the properties of materials. Based on the radiation behavior, the engineering materials are categorized into two different types. The first one comprises organic solids which are sensitive to the energy deposited in their electronic system and the second one comprises metals which are insensitive to the energy deposited in their electronic system. However, exposure to swift heavy ions alters this general behavior. Depending on the mass, kinetic energy and nuclear charge, an ion can produce modifications within a thin surface layer or it can penetrate deeply to produce long and narrow distorted area along its path. When a high energetic ion beam impinges on a material, it causes two different types of changes in the material due to the columbic interaction between the target atom and the energetic ion beam: (i) inelastic collisions of the energetic ion with the atomic electrons of the material; and (ii) elastic scattering from the nuclei of the atoms of the material, which is extremely responsible for relocating the atoms of matter from their lattice position. The exposure of the heavy ions renders the material return to equilibrium state during which the material undergoes surface and bulk modifications which depends on the mass of the projectile ion, physical properties of the target material, its energy, and beam dimension. It is well established that electronic stopping power plays a major role in the defect creation mechanism provided it exceeds a threshold which strongly depends on the nature of the target material. There are reports available on heavy ion irradiation especially on crystalline materials to tune their physical and chemical properties. L-Arginine Acetate [LAA] is a potential semi-organic nonlinear optical crystal and its optical, mechanical and thermal properties have already been reported The main objective of the present work is to enhance or tune the structural and optical properties of LAA single crystals by heavy ion irradiation. In the present study, a potential nonlinear optical single crystal, L-arginine acetate (LAA) was grown by slow evaporation solution growth technique. The grown LAA single crystal was irradiated with oxygen ions at the dose rate of 600 krad and 1M rad in order to tune the structural and optical properties. The structural properties of pristine and oxygen ions irradiated LAA single crystals were studied using Powder X- ray diffraction and Fourier Transform Infrared spectral studies which reveal the structural changes that are generated due to irradiation. Optical behavior of pristine and oxygen ions irradiated crystals is studied by UV-Vis-NIR and photoluminescence analyses. From this investigation we can concluded that oxygen ions irradiation modifies the structural and optical properties of LAA single crystals.

Keywords: heavy ion irradiation, NLO single crystal, photoluminescence, X-ray diffractometer

Procedia PDF Downloads 227

Authors: K. Ghosh, S. N. Tripathi, Manish Joshi, Y. S. Mayya, Arshad Khan, B. K. Sapra

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We have developed a CFD coupled aerosol microphysics model in the context of aerosol generation from a glowing wire. The governing equations can be solved implicitly for mass, momentum, energy transfer along with aerosol dynamics. The computationally efficient framework can simulate temporal behavior of total number concentration and number size distribution. This formulation uniquely couples standard K-Epsilon scheme with boundary layer model with detailed aerosol dynamics through residence time. This model uses measured temperatures (wire surface and axial/radial surroundings) and wire compositional data apart from other usual inputs for simulations. The model predictions show that bulk fluid motion and local heat distribution can significantly affect the aerosol behavior when the buoyancy effect in momentum transfer is considered. Buoyancy generated turbulence was found to be affecting parameters related to aerosol dynamics and transport as well. The model was validated by comparing simulated predictions with results obtained from six controlled experiments performed with a laboratory-made hot wire nanoparticle generator. Condensation particle counter (CPC) and scanning mobility particle sizer (SMPS) were used for measurement of total number concentration and number size distribution at the outlet of reactor cell during these experiments. Our model-predicted results were found to be in reasonable agreement with observed values. The developed model is fast (fully implicit) and numerically stable. It can be used specifically for applications in the context of the behavior of aerosol particles generated from glowing wire technique and in general for other similar large scale domains. Incorporation of CFD in aerosol microphysics framework provides a realistic platform to study natural convection driven systems/ applications. Aerosol dynamics sub-modules (nucleation, coagulation, wall deposition) have been coupled with Navier Stokes equations modified to include buoyancy coupled K-Epsilon turbulence model. Coupled flow-aerosol dynamics equation was solved numerically and in the implicit scheme. Wire composition and temperature (wire surface and cell domain) were obtained/measured, to be used as input for the model simulations. Model simulations showed a significant effect of fluid properties on the dynamics of aerosol particles. The role of buoyancy was highlighted by observation and interpretation of nucleation zones in the planes above the wire axis. The model was validated against measured temporal evolution, total number concentration and size distribution at the outlet of hot wire generator cell. Experimentally averaged and simulated total number concentrations were found to match closely, barring values at initial times. Steady-state number size distribution matched very well for sub 10 nm particle diameters while reasonable differences were noticed for higher size ranges. Although tuned specifically for the present context (i.e., aerosol generation from hotwire generator), the model can also be used for diverse applications, e.g., emission of particles from hot zones (chimneys, exhaust), fires and atmospheric cloud dynamics.

Keywords: nanoparticles, k-epsilon model, buoyancy, CFD, hot wire generator, aerosol dynamics

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Authors: Ahmed Tawfik

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Oxidation of 1,4 dioxane produces metabolites by-products involving glycolaldehyde and acids that have geno- and cytotoxicity impact on microbial degradation. Thereby, the incorporation of algae with bacteria in the treatment system would eliminate and overcome the accumulation of metabolites that are utilized as a carbon source for the build-up of biomass. Therefore, the aim of the present study is to assess the potential of algae/bacteria-based membrane bioreactor (AB-MBR) for biodegradation of 1,4 dioxane-rich wastewater at a high imposed loading rate. Three identical reactors, i.e., AB-MBR1, AB-MBR2, and AB-MBR3, were operated in parallel at 1,4 dioxane loading rates of 641.7, 320.9, and 160.4 mg/L. d., and HRTs of 6.0, 12 and 24 h. respectively. The AB-MBR1 achieved 1,4 dioxane removal rate of 263.7 mg/L.d., where the residual value in the treated effluent amounted to 94.4±22.9 mg/L. Reducing the 1,4 dioxane loading rate (LR) to 320.9 mg/L.d in the AB-MBR2 maximized the removal rate efficiency of 265.9 mg/L.d., with a removal efficiency of 82.8±3.2%. The minimum value of 1,4 dioxane of 17.3±1.8 mg/L in the treated effluent of AB-MBR3 was obtained at an HRT of 24.0 h and loading rate of 160.4 mg/L.d. The mechanism of 1,4 dioxane degradation in AB-MBR was a combination of volatilization (8.03±0.6%), UV oxidation (14.1±0.9%), microbial biodegradation (49.1±3.9%) and absorption/uptake and assimilation by algae (28.8±2.%). Further, the Thioclava, Afipia, and Mycobacterium genera oxidized and produced the required enzymes for hydrolysis and cleavage of the dioxane ring into 2-hydroxy-1,4 dioxane. Moreover, the fungi, i.e., Basidiomycota and Cryptomycota, played a big role in the degradation of the 1,4 dioxane into 2-hydroxy-1,4 dioxane. Xanthobacter and Mesorhizobium were involved in the metabolism process by secreting alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH), and glycolate oxidase. Bacteria and fungi produced dehydrogenase (DH) for the transformation of 2-hydroxy-1,4 dioxane into 2-hydroxy-ethoxyacetaldehyde. The latter is converted into Ethylene glycol by Aldehyde hydrogenase (ALDH). Ethylene glycol is oxidized into acids using Alcohol hydrogenase (ADH). The Diatomea, Chlorophyta, and Streptophyta utilize the metabolites for biomass assimilation and produce the required oxygen for further oxidation of the dioxane and its metabolites by-products of bacteria and fungi. The major portion of metabolites (ethylene glycol, glycolic acid, and oxalic acid were removed due to uptake and absorption by algae (43±4.3%), followed by adsorption (18.4±0.9%). The volatilization and UV oxidation contribution for the degradation of metabolites were 8.7±0.7% and 12.3±0.8%, respectively. The capabilities of genera Defluviimonas, Thioclava, Luteolibacter, and Afipia. The genera of Defluviimonas, Thioclava, Luteolibacter, and Mycobacterium were grown under a high 1,4 dioxane LR of 641.7 mg/L.d. The Chlorophyta (4.1-43.6%), Streptophyta (2.5-21.7%), and Diatomea (0.8-1.4%) phyla were dominant for degradation of 1,4 dioxane. The results of this study strongly demonstrated that the bioremediation and bioaugmentation process can safely remove 1,4 dioxane from industrial wastewater while minimizing environmental concerns and reducing economic costs.

Keywords: wastewater, membrane bioreactor, bacterial community, algal community

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Authors: Ching Shya Lee, Mohamed Kheireddine Aroua, Wan Mohd Ashri Wan Daud, Patrick Cognet, Yolande Peres, Mohammed Ajeel

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In recent years, with the decreasing supply of fossil fuel, renewable energy has received a significant demand. Biodiesel which is well known as vegetable oil based fatty acid methyl ester is an alternative fuel for diesel. It can be produced from transesterification of vegetable oils, such as palm oil, sunflower oil, rapeseed oil, etc., with methanol. During the transesterification process, crude glycerol is formed as a by-product, resulting in 10% wt of the total biodiesel production. To date, due to the fast growing of biodiesel production in worldwide, the crude glycerol supply has also increased rapidly and resulted in a significant price drop for glycerol. Therefore, extensive research has been developed to use glycerol as feedstock to produce various added-value chemicals, such as tartronic acid, mesoxalic acid, glycolic acid, glyceric acid, propanediol, acrolein etc. The industrial processes that usually involved are selective oxidation, biofermentation, esterification, and hydrolysis. However, the conversion of glycerol into added-value compounds by electrochemical approach is rarely discussed. Currently, the approach is mainly focused on the electro-oxidation study of glycerol under potentiostatic mode for cogenerating energy with other chemicals. The electro-organic synthesis study from glycerol under galvanostatic mode is seldom reviewed. In this study, the glycerol was converted into various added-value compounds by electrochemical method under galvanostatic mode. This work aimed to study the possible compounds produced from glycerol by electrochemical technique in a one-pot electrolysis cell. The electro-organic synthesis study from glycerol was carried out in a single compartment reactor for 8 hours, over the platinum cathode and anode electrodes under acidic condition. Various parameters such as electric current (1.0 A to 3.0 A) and reaction temperature (27 °C to 80 °C) were evaluated. The products obtained were characterized by using gas chromatography-mass spectroscopy equipped with an aqueous-stable polyethylene glycol stationary phase column. Under the optimized reaction condition, the glycerol conversion achieved as high as 95%. The glycerol was successfully converted into various added-value chemicals such as ethylene glycol, glycolic acid, glyceric acid, acetaldehyde, formic acid, and glyceraldehyde; given the yield of 1%, 45%, 27%, 4%, 0.7% and 5%, respectively. Based on the products obtained from this study, the reaction mechanism of this process is proposed. In conclusion, this study has successfully converted glycerol into a wide variety of added-value compounds. These chemicals are found to have high market value; they can be used in the pharmaceutical, food and cosmetic industries. This study effectively opens a new approach for the electrochemical conversion of glycerol. For further enhancement on the product selectivity, electrode material is an important parameter to be considered.

Keywords: biodiesel, glycerol, electrochemical conversion, galvanostatic mode

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Authors: Jesus Carretero, Mario Vasile, Guillermo Izquierdo, Javier Garcia-Blas

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Currently, there is a so called ‘identity crisis’ in cybersecurity caused by the substantial security, privacy and usability shortcomings encountered in existing systems for identity management. Federated Identity Management (FIM) could be solution for this crisis, as it is a method that facilitates management of identity processes and policies among collaborating entities without enforcing a global consistency, that is difficult to achieve when there are ID legacy systems. To cope with this problem, the Connecting Europe Facility (CEF) initiative proposed in 2014 a federated solution in anticipation of the adoption of the Regulation (EU) N°910/2014, the so-called eIDAS Regulation. At present, a network of eIDAS Nodes is being deployed at European level to allow that every citizen recognized by a member state is to be recognized within the trust network at European level, enabling the consumption of services in other member states that, until now were not allowed, or whose concession was tedious. This is a very ambitious approach, since it tends to enable cross-border authentication of Member States citizens without the need to unify the authentication method (eID Scheme) of the member state in question. However, this federation is currently managed by member states and it is initially applied only to citizens and public organizations. The goal of this paper is to present the results of a European Project, named eID@Cloud, that focuses on the integration of eID in 5 cloud platforms belonging to authentication service providers of different EU Member States to act as Service Providers (SP) for private entities. We propose an initiative based on a private eID Scheme both for natural and legal persons. The methodology followed in the eID@Cloud project is that each Identity Provider (IdP) is subscribed to an eIDAS Node Connector, requesting for authentication, that is subscribed to an eIDAS Node Proxy Service, issuing authentication assertions. To cope with high loads, load balancing is supported in the eIDAS Node. The eID@Cloud project is still going on, but we already have some important outcomes. First, we have deployed the federation identity nodes and tested it from the security and performance point of view. The pilot prototype has shown the feasibility of deploying this kind of systems, ensuring good performance due to the replication of the eIDAS nodes and the load balance mechanism. Second, our solution avoids the propagation of identity data out of the native domain of the user or entity being identified, which avoids problems well known in cybersecurity due to network interception, man in the middle attack, etc. Last, but not least, this system allows to connect any country or collectivity easily, providing incremental development of the network and avoiding difficult political negotiations to agree on a single authentication format (which would be a major stopper).

Keywords: cybersecurity, identity federation, trust, user authentication

Procedia PDF Downloads 144

Authors: Victor Mantilla, Romeu Vicente, António Figueiredo, Victor Ferreira, Sandra Sorte

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Integrating dynamic facades into contemporary building design is shaping a new era of energy efficiency and user comfort. These innovative facades, often constructed using lightweight construction systems and materials, offer an opportunity to have a responsive and adaptive nature to the dynamic behavior of the outdoor climate. Therefore, in regions characterized by high fluctuations in daily temperatures, the ability to adapt to environmental changes is of paramount importance and a challenge. This paper presents a thorough review of the state of the art on double-skin facades (DSF), focusing on lightweight solutions for the external envelope. Dynamic facades featuring elements like movable shading devices, phase change materials, and advanced control systems have revolutionized the built environment. They offer a promising path for reducing energy consumption while enhancing occupant well-being. Lightweight construction systems are increasingly becoming the choice for the constitution of these facade solutions, offering benefits such as reduced structural loads and reduced construction waste, improving overall sustainability. However, the performance of dynamic facades based on low thermal inertia solutions in climatic contexts with high thermal amplitude is still in need of research since their ability to adapt is traduced in variability/manipulation of the thermal transmittance coefficient (U-value). Emerging technologies can enable such a dynamic thermal behavior through innovative materials, changes in geometry and control to optimize the facade performance. These innovations will allow a facade system to respond to shifting outdoor temperature, relative humidity, wind, and solar radiation conditions, ensuring that energy efficiency and occupant comfort are both met/coupled. This review addresses the potential configuration of double-skin facades, particularly concerning their responsiveness to seasonal variations in temperature, with a specific focus on addressing the challenges posed by winter and summer conditions. Notably, the design of a dynamic facade is significantly shaped by several pivotal factors, including the choice of materials, geometric considerations, and the implementation of effective monitoring systems. Within the realm of double skin facades, various configurations are explored, encompassing exhaust air, supply air, and thermal buffering mechanisms. According to the review places a specific emphasis on the thermal dynamics at play, closely examining the impact of factors such as the color of the facade, the slat angle's dimensions, and the positioning and type of shading devices employed in these innovative architectural structures.This paper will synthesize the current research trends in this field, with the presentation of case studies and technological innovations with a comprehensive understanding of the cutting-edge solutions propelling the evolution of building envelopes in the face of climate change, namely focusing on double-skin lightweight solutions to create sustainable, adaptable, and responsive building envelopes. As indicated in the review, flexible and lightweight systems have broad applicability across all building sectors, and there is a growing recognition that retrofitting existing buildings may emerge as the predominant approach.

Keywords: adaptive, control systems, dynamic facades, energy efficiency, responsive, thermal comfort, thermal transmittance

Procedia PDF Downloads 45

Authors: Jeanne Leblond, Warren Viricel, Amira Mbarek

Abstract:

Although several products have reached the market, gene therapeutics are still in their first stages and require optimization. It is possible to improve their lacking efficiency by the use of carefully engineered vectors, able to carry the genetic material through each of the biological barriers they need to cross. In particular, getting inside the cell is a major challenge, because these hydrophilic nucleic acids have to cross the lipid-rich plasmatic and/or endosomal membrane, before being degraded into lysosomes. It takes less than one hour for newly endocytosed liposomes to reach highly acidic lysosomes, meaning that the degradation of the carried gene occurs rapidly, thus limiting the transfection efficiency. We propose to use a new pH-sensitive lipid able to change its conformation upon protonation at endosomal pH values, leading to the disruption of the lipidic bilayer and thus to the fast release of the nucleic acids into the cytosol. It is expected that this new pH-sensitive mechanism promote endosomal escape of the gene, thereby its transfection efficiency. The main challenge of this work was to design a preparation presenting fast-responding lipidic bilayer destabilization properties at endosomal pH 5 while remaining stable at blood pH value and during storage. A series of pH-sensitive lipids able to perform a conformational switch upon acidification were designed and synthesized. Liposomes containing these switchable lipids, as well as co-lipids were prepared and characterized. The liposomes were stable at 4°C and pH 7.4 for several months. Incubation with siRNA led to the full entrapment of nucleic acids as soon as the positive/negative charge ratio was superior to 2. The best liposomal formulation demonstrated a silencing efficiency up to 10% on HeLa cells, very similar to a commercial agent, with a lowest toxicity than the commercial agent. Using flow cytometry and microscopy assays, we demonstrated that drop of pH was required for the transfection efficiency, since bafilomycin blocked the transfection efficiency. Additional evidence was brought by the synthesis of a negative control lipid, which was unable to switch its conformation, and consequently exhibited no transfection ability. Mechanistic studies revealed that the uptake was mediated through endocytosis, by clathrin and caveolae pathways, as reported for previous lipid nanoparticle systems. This potent system was used for the treatment of hypercholesterolemia. The switchable lipids were able to knockdown PCSK9 expression on human hepatocytes (Huh-7). Its efficiency is currently evaluated on in vivo mice model of PCSK9 KO mice. In summary, we designed and optimized a new cationic pH-sensitive lipid for gene delivery. Its transfection efficiency is similar to the best available commercial agent, without the usually associated toxicity. The promising results lead to its use for the treatment of hypercholesterolemia on a mice model. Anticancer applications and pulmonary chronic disease are also currently investigated.

Keywords: liposomes, siRNA, pH-sensitive, molecular switch

Procedia PDF Downloads 184